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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1378634

Synergistic Anti-osteoporosis Effects of Anemarrhena Asphodeloides Bunge-Phellodendron Chinense C.K. Schneid Herb Pair via Ferroptosis Suppression in Ovariectomized Mice

Provisionally accepted
Xuehui Deng Xuehui Deng 1,2Wenlong Xiao Wenlong Xiao 3Bingfeng Lin Bingfeng Lin 1Fang Wang Fang Wang 2Li Song Li Song 1Nani Wang Nani Wang 1,2,3*
  • 1 Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
  • 2 Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 3 Hangzhou Medical College, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Ferroptosis plays a crucial role in the progression of postmenopausal osteoporosis. Anemarrhena asphodeloides Bunge/Phellodendron chinense C.K. Schneid (AA/PC) is the core herb pair in traditional Chinese medicines formulae for postmenopausal osteoporosis treatment. However, the synergistic effects, and mechanisms, of AA/PC on alleviating ferroptosis and postmenopausal osteoporosis remain unclear. The goal herein was to analyze the effective ingredients and molecular mechanisms of AA/PC in the treatment of osteoporosis through serum pharmacochemistry, network pharmacology, metabolomics analysis, and pharmacodynamics evaluation. A bilateral ovariectomized (OVX) mouse model was established. Micron-scale computed tomography analysis showed that AA/PC increased bone mineral density in OVX mice. The effects of AA/PC were better than AA or PC alone on inhibiting the bone resorption marker nuclear factor of activated T-cells 1. Furthermore, five absorbable compounds were detected in serum: mangiferin, magnoflorine, berberine, timosaponin BIII, and timosaponin AIII. Network pharmacology showed these compounds had close relationship with seven ferroptosis targets. Importantly, compared with AA or PC alone, the AA/PC herb pair exerted better effects on regulating crucial ferroptosis pathways, including the system xc-/glutathione/glutathione peroxidase 4, transferrin receptor/ferritin, and acyl-CoA synthetase long chain family member 4/polyunsaturated fatty acids signaling pathways. These results indicate that AA/PC exerts synergistic effects on regulating glutathione synthesis, iron homeostasis, and lipid metabolism in ferroptosis. This work lays the foundation for further development and use of AA/PC herb pair for preventing and treating postmenopausal osteoporosis.

    Keywords: Anemarrhena asphodeloides Bunge, Phellodendron chinense C.K.Schneid., Herb pair, Osteoporosis, ferroptosis

    Received: 30 Jan 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Deng, Xiao, Lin, Wang, Song and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nani Wang, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, 310000, Zhejiang Province, China

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